The Cache County Dementia Progression Study (CC-DPS) has followed one of a few population based samples of incident dementia, consisting of individuals characterized before their dementia onset. The project utilizes pre-morbid health and genetic and environmental risk factor information to determine their effects on the progression of cognitive, functional and behavioral trajectories. Key discoveries include: a) 30% of cases are "slow decliners," b) neuropsychiatric symptoms occur in clusters, c) vascular factors, their treatments, and the care environment modify progression, and d) the APOE e4 allele modifies the effects of other factors. In its next phase, CC-DPS proposes to examine hypothesized mechanisms underlying some of the above observations, clarify the role of APOE e4 on the course of dementia progression, examine how medical co-morbidities as well as the use of medications and supplements affects the rate of progression and disease duration, and to expand understanding of the interrelated nature of the cognitive, functional and behavioral trajectories of dementia. The specific aims are to: 1) Clarify whether the association between APOE e4 and dementia progression varies according to dementia severity and duration; 2) Examine whether lifetime medical co-morbidities and exposure to antioxidant and anti-inflammatory compounds accelerate or attenuate dementia progression and whether their effects are modified by APOE genotype; 3) Examine whether strategies to build cognitive reserve after the onset of dementia are associated with slower progression; 4) Examine the effects of modifiable factors on the emergence and persistence of behavioral symptoms and symptom clusters; 5) Examine putative mechanisms underlying the relationship between the care environment and dementia progression;and 6) Characterize the interacting nature of domain trajectories in dementia. To support these aims, the study will continue to follow the remaining participants and their caregivers for an additional 1.5 years to increase person years of observation. Principal measures of progression include: a cognitive battery, Clinical Dementia Rating Scale, Neuropsychiatric Inventory, Cornell Scale for Depression in Dementia, time to institutionalization, quality of life ratings, and mortality. This project is the first population-based study of caregiving effects on dementia progression, and with the examination of a rich array of modifiable risk factors, the study has the potential to advance our understanding of the epidemiology of behavioral symptoms in dementia and the factors that contribute to clinical variation in disease course. At CC-DPS completion, we will 1) advance understanding of dementia progression and prognosis;2) discover factors that modify its course;and 3) identify potential new avenues for effective interventions.